Effects of carboplatin on the testis. A histological study

In the present study, the influence of carboplatin [diammine(cyclobutane-1,1-dicarboxylato)platinum(II)], the main and most active representative of second-generation antitumour platinum complexes, on the morphology of the testes of male CF1 mice was investigated histologically by examining semithick sections. Carboplatin was administered in doses of 30, 60, or 120 mg/kg and applied as a single intraperitoneal injection. For comparison purposes, the parent compound cisplatin [cis-diamminedichloroplatinum(II)] was administered at equitoxic doses (3, 6 or 12 mg/kg). At various intervals between days 1 and 28 after treatment, the testes were removed and embedded in Epon. Both compounds effected severe structural alterations of Sertoli cells, disrupted the blood/testis barrier, and impaired the processes both of spermatogenesis and spermiohistogenesis. The structural damage in the testes following treatment with carboplatin was at least as pronounced as that occurring under the influence of equitoxic doses of cisplatin. Within a few days, the intercellular spaces around Sertoli cells widened, the tight contacts with neighbouring cells were disrupted, the cytoplasm of Sertoli cells disintegrated and their nuclei shrank. Numerous necroses, abnormal mitotic figures of spermatogenic cells and malformed spermatozoa appeared. Severe damage was evident on days 10-21 after treatment with carboplatin, the strength of the symptoms being clearly dependent on the dose applied. The first indications of ongoing recovery processes were detected on day 21 in the case of the low dose (30 mg/kg) or on day 28 following treatment with 60 mg/kg or 120 mg/kg. These results confirm that carboplatin is at least as toxic to the testes as cisplatin and that its substitution for cisplatin in clinical therapy does not diminish the problem of drug-induced infertility following platinum-based chemotherapy.